星形胶质细胞吞噬受体MERTK在应激性认知功能障碍中的变化及其作用

Changes and roles of astrocyte phagocytic receptor MERTK in stress cognitive dysfunction

目的观察慢性应激下星形胶质细胞吞噬受体的变化,探讨慢性应激致认知功能障碍的可能机制。方法采用慢性束缚应激(CRS)建立应激致认知功能障碍大鼠模型,利用旷场、新旧物体识别、水迷宫实验检测大鼠行为学表现,通过ELISA法检测应激激素糖皮质激素(GC)水平,Western印迹、实时荧光定量PCR(qRT-PCR)法检测不同脑区MER原癌基因酪氨酸激酶(MERTK)和突触素(SYP)表达水平,免疫荧光法检测海马SYP表达情况。结果与Ctrl组相比,CRS组大鼠血清和脑脊液中GC水平显著升高(P<0.05),旷场实验得分、物体识别指数、水迷宫空间探索实验得分显著降低(P<0.05),各脑区MERTK表达水平显著升高(P<0.05)、突触结构标志物SYP表达显著降低(P<0.05)。结论慢性应激诱导星形胶质细胞吞噬受体MERTK表达升高,突触结构标志物SYP表达下调,可能是MERTK升高引起吞噬功能异常致SYP下调,进而发生应激性认知功能障碍。

Objective To observe the changes in astrocyte phagocyte receptors under chronic stress and explore the possible mechanism of cognitive dysfunction induced by chronic stress.Methods Chronic restraint stress(CRS)was used to establish a rat model of cognitive dysfunction induced by stress.The open field test,objective recognition test and water maze experiment were used to observe rats′behavioral performance.The ELISA method was used for the detection of concentrations of serum stress hormones GC.Western blotting and quantitative real-time polymerase chain reaction(qRTPCR)were used to detect transcription/translation levels of MERTK and SYP in different areas of the brain.Immunofluorescence was used to detect the expression of SYP in the hippocampus.Results Compared with the Ctrl group,serum and cerebrospinal fluid stress hormone GC levels in the CRS group increased(P<0.05),while the open field score,objective cognitive index,and score of spatial probe of water maze decreased(P<0.05).Transcription/translation levels of MERTK in each area of the brain increased(P<0.05),while synaptic structure markers,and synaptophysin decreased(P<0.05).Conclusion Chronic stress induces elevated expressions of astrocyte phagocytic receptor MERTK and downregulated expressions of the synaptic structural marker SYP,which may be due to abnormal phagocytic function caused by elevated MERTK.